News Statement
15 September 2022 on Thursday
A research team supported by the National Institutes of Health has demonstrated that commercially accessible fast antigen testing may detect past and present variants of concern, as well as identified possible mutations that may affect future test performance. Concerns have been raised over the efficacy of fast antigen tests as novel SARS-CoV-2 viral variants continue to emerge.
The team, which was supported by the NIH’s Rapid Acceleration of Diagnostics (RADx®) Tech initiative, devised a method for determining how alterations to SARS-CoV-2 affect detection by antibodies used in rapid antigen assays. Since most rapid antigen tests detect the SARS-CoV-2 nucleocapsid protein, or N protein, the team measured directly how alterations to the N protein affected the ability of diagnostic antibodies to recognize their target.
“Rapid antigen tests remain an important COVID-19 mitigation tool, and it is essential to ensure that these tests can detect the SARS-CoV-2 virus as it continues to evolve,” said Bruce J. Tromberg, Ph.D., director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and lead for the RADx Tech program at the National Institutes of Health (NIH). Due to the never-ending cycle of novel varieties, the data from this study will be helpful for many years.
The research, which was reported in Cell, employed a technique known as deep mutational scanning to assess simultaneously how a single amino acid variation in the N protein could affect diagnostic antibody binding. The researchers created a comprehensive library of N protein variants, which includes nearly 8,000 single amino acid substitutions – representing more than 99.5% of all possible mutations – and evaluated their interaction with 17 distinct diagnostic antibodies utilized in 11 commercially available rapid antigen tests. Rapid antigen testing frequently utilize two distinct diagnostic antibodies to detect the SARS-CoV-2 infection.
For each tested diagnostic antibody, the researchers recorded which N-protein mutations influenced antibody recognition. Based on this data, they produced a “escape mutation profile” for each antibody, which details the exact alterations to the N protein that affect the antibody’s ability to attach to its target. Despite the fact that many diagnostic antibodies detected the same area of the N protein, the researchers discovered that each antibody possessed a distinct escape mutation profile. As the SARS-CoV-2 virus continues to undergo changes, this information can be used to identify specific antibodies whose diagnostic performance may require reevaluation.
“According to our findings, none of the major previous and present SARS-CoV-2 variants of concern contain N protein mutations that would compromise detection by antibodies employed in current quick antigen tests,” stated Filipp Frank, Ph.D., assistant professor of biochemistry at Emory University in Atlanta. “Furthermore, this information could assist test design by indicating which diagnostic antibodies should be matched to detect the greatest number of possible N protein variants.”
“Accurate and efficient identification of infected individuals remains a critically important strategy for COVID-19 mitigation,” said Eric Ortlund, Ph.D., a professor in the department of biochemistry at Emory University. “Our study provides information about future SARS-CoV-2 mutations that may interfere with detection.” “The insights presented here will allow us to quickly adjust to the virus as new varieties continue to arise, having an immediate impact on clinical and public health.”
Despite the fact that numerous variations of concern contain multiple mutations to the N protein, the authors of the study caution that their method does not analyze how multiple mutations can influence diagnostic antibody identification, which is a drawback of the study.
The project was partially sponsored by American Rescue Plan Act of 2021 funds handled by NIBIB under award numbers U54EB015408 and U54EB027690. Additionally, the work was financed by award number 75N92019P00328. This support was provided as part of the RADx program, which was designed to accelerate innovation in the development, commercialization, and application of COVID-19 testing technologies.
Researchers were also sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (grant number R01DK115213), the National Institute of Allergy and Infectious Diseases (grant number K99AI153736), and the American Heart Association (grant number 848388) for career development.
About the initiative Rapid Acceleration of Diagnostics (RADx®):
The RADx program was started on April 29, 2020, with the objective of accelerating innovation in the development, commercialization, and application of COVID-19 testing technology. RADx Tech, RADx Advanced Technology Platforms, RADx Underserved Populations, and RADx Radical are the initiative’s four programs. It utilizes the existing Point-of-Care Technology Research Network of the NIH. The Office of the Assistant Secretary of Health, the Department of Defense, the Biomedical Advanced Research and Development Authority, and the U.S. Food and Drug Administration are collaborators with the RADx effort. Explore the RADx initiative and its associated programs at https://www.nih.gov/radx.
The National Institute of Biomedical Imaging and Bioengineering (NIBIB) was established in 1988.
The objective of NIBIB is to promote health by driving the development of biomedical technologies and expediting their use. To enhance basic research and medical care, the Institute is committed to merging the physical and engineering sciences with the life sciences. NIBIB promotes research and development of emerging technologies in its internal laboratories and through grants, partnerships, and training. NIBIB’s website, https://www.nibib.nih.gov, contains additional information.
NIH stands for the National Institutes of Health. The National Institutes of Health (NIH), the nation’s medical research organization, consists of 27 Institutes and Centers and is part of the U.S. Department of Health and Human Services. The NIH is the principal government organization that conducts and supports basic, clinical, and translational medical research and investigates the causes, treatments, and cures for both common and rare diseases. Visit www.nih.gov for more information on the NIH and its initiatives.
NIH…Transforming Research Into Health®
References
Xu Liu, Heather B. Bowers, Anamika B. Patel, Michael L. Cato, Julie A. Sullivan, Morgan Greenleaf, Anne Piantadosi, Wilbur A. Lam, William H. Hudson, and Eric A. Ortlund. Deep mutational scanning identifies SARS-CoV-2 Nucleocapsid escape mutations in quick antigen tests currently available. Cell 2022. https://doi.org/10.1016/j.cell.2022.08.010.
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